Particle-based science and technology is an important aspect of biomedical and clinical research. Inorganic particles such as quantum dots and beads have found applications in bio-imaging and point-of-care diagnosis. These particles can further be conjugated with other materials such as proteins or DNAs for biosensors and bioassays. Living particles such as cells, viruses and bacteria are commonplace in everyday biological experiments. Through analysis of their molecular and cellular properties using techniques such as DNA sequencing, protein mapping and high content screening, these particles have greatly advanced the development of the biological sciences.
The most common particle analysis apparatus is the flow cytometer, where particles with fluorescent tags are hydrodynamically focused into a stream and excited by laser beams. The emitted fluorescence from the tags are collected by photodetectors and analyzed to extrapolate information about the biological properties of each individual particle. There are three major drawbacks of the system: 1) the system is expensive and bulky. 2) the particles can not be analyzed over time due to the single pass nature of the flow cytometer. 3) it does not resolve subcellular localization of fluorescent signals.
In order to conduct detailed analysis of the particles, it is desired to trap these particles in specific locations so they don't displace due to the forces of fluid flow, shear stress or thermal agitation during the course of the experiment. Microfluidic devices are ideal candidates for particle analysis because of their compact size, low reagent consumption and laminar flow nature. One common method of trapping particles is to use dielectrophoresis, where electrodes and electric fields are used to generate dielectrophoretic forces on particles; however, the particles trapped using this method can still rotate, and are subject to displacement when flows are introduced. In addition, the fabrication of electrodes into the device significantly increases the cost. Using a sieve at a size smaller than the particles can serve as a particle trap; however, the particles will be packed into clumps, making it difficult to analyze.
The potential advantages of a trapped particle array device have been realized to a limited extent in the prior art. Various limitations associated with prior art devices include (i) difficulty in preventing microfluidic structures from being blocked by particles within the structures, (ii) inability to trap the particles so they won't be displaced by fluidic flows, (iii) inability to provide different solutions to the particles at different times for rapid assay.
It would therefore be desirable to provide a microfluidic particle trapping device capable of more fully realizing the advantages noted above in a high throughput particle analysis system.